Skip to main content
SpringerLink
Log in

Polycyclic Aromatic Hydrocarbon-DNA Adducts in Smokers and Their Relationship to Micronutrient Levels and Glutathione-S-Transferase M1 Genotype

  • Chapter
Book cover Nutrients in Cancer Prevention and Treatment

Part of the book series: Experimental Biology and Medicine ((EBAM,volume 27))

  • 94 Accesses

Abstract

Sixty-three male cigarette smokers were entered into a cross-sectional study to determine whether inverse associations existed between polycyclic aromatic hydrocarbon (PAH)-DNA adduct levels and intake/serum levels of vitamin A, vitamin C and vitamin E. Associations between PAH-DNA adducts and intakes of carotene as well as serum levels of (β-carotene were also determined. Fasting blood samples were collected for assays of PAH-DNA adducts in circulating mononuclear cells, plasma cotinine and serum levels of vitamin A, β-carotene, vitamin C and vitamin E. Since genetic deficiency in the detoxifying enzyme glutathione S-transferase M1 (GSTM1) has been associated with increased risk of lung cancer, GSTM1 genotype was also determined. Analysis of PAH-DNA adducts by competitive enzyme-linked immunosorbent assay (ELISA) indicated that 70% of the subjects had detectable adducts with a mean of 4.38 adducts/108 nucleotides (range 1.00-24.1/108). Pearson’s method was utilized to determine whether any associations existed between the various host variables and PAH-DNA adducts. Previously, no significant associations were found between PAH-DNA adducts and cigarettes smoked/day, pack-years, daily/lifetime tar exposures or plasma cotinine levels [Carcinogenesis 13:2041,1992]. PAH-DNA adducts were inversely associated with serum cholesterol-adjusted vitamin E levels (r=-0.25, p≤0.05) and with smoking-adjusted vitamin C serum levels (r=-0.22, p<_0.09). Stratification by GSTM1 genotype indicated that these associations were limited to subjects with the null genotype. The relationship between adducts and serum cholesterol-adjusted vitamin E was significant in those of the null genotype (r=-0.38, p≤0.04) but not in those with the gene present (r=-0.12, p=0.5). Similarly, for smoking-adjusted vitamin C, the relationship with adducts was stronger in subjects with the null genotype (r=-0.35, p≤0.06) than in those with GSTM1 present (r=-0.05, p=0.77). These results are consistent with findings of prior epidemiological studies identifying significant inverse associations between antioxidant micronutrient status or GSTM1 genotype and the incidence of lung cancer. Additional studies should be conducted to confirm a possible protective role for vitamin E in PAH-DNA adduct formation and to explore further the possible roles of vitamin A, ß-carotene and vitamin C in modulating adduct formation and lung cancer risk.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Rom WN: “Environmental and occupational medicine.” Little Brown and Co.,Boston, MA, 1992.

    Google Scholar 

  2. Grunberger D, Singer B: “Molecular Biology of Mutagens and Carcinogens.” New York: Plenum, 1983

    Google Scholar 

  3. Perera FP, Santella RM, Brenner D, Poirier MC, Munshi AA, Fischman HK, VanRyzin J: DNA adducts, protein adducts and SCE in cigarette smokers and nonsmokers. J Natl Cancer Inst 79:449–456, 1987.

    CAS  Google Scholar 

  4. Jahnke GD, Thompson CL, Walker MP, Gallagher JE, Lucier GW, DiAugustine RP: Multiple DNA adducts in lymphocytes of smokers and nonsmokers determined by [32P]-postlabeling analysis. Carcinogenesis 11:205–211, 1990.

    Article  CAS  Google Scholar 

  5. Santella RM, Grinberg-Funes RA, Young TL, Dickey C, Singh VN, Wang LW, Perera FP: Cigarette smoking related polycyclic aromatic hydrocarbon-DNA adducts in peripheral mononuclear cells. Carcinogenesis 13:2041–2045, 1992.

    Article  CAS  Google Scholar 

  6. Shamsuddin AKM, Sinopoli NT, Hemminki K, Boesch RB, Harris CC: Detection of benzo[a]pyrene: DNA adducts in human white blood cells. Cancer Res 45:66–68, 1985.

    CAS  Google Scholar 

  7. Perera FP, Hemminki K, Young TL, Santella RM, Brenner D, and Kelly, G: Detection of polycyclic aromatic hydrocarbon-DNA adducts in white blood cells of foundry workers. Cancer Res 48:2288–2291, 1988.

    CAS  Google Scholar 

  8. Harris CC, Vahakangas K, Newman MJ, Trivers GE, Shamsuddin A, Sinopoli N, Mann DL, Wright WE: Detection of benzo[a]pyrene diol epoxide-DNA adducts in peripheral blood lymphocytes and antibodies to the adducts in serum from coke oven workers. Proc Natl Acad Sci USA 82:6672–6676, 1985.

    Article  CAS  Google Scholar 

  9. Perera FP, Hemminki K, Grzybowska E, Motykiewiez G, Santella RM, Young TL, Dickey C, Brandt-Rauf P, DeVivo I, Blaner B, Tsai W, Chorazy M: Molecular damage from environmental pollution in Poland. Nature (London) 360:256–258, 1992.

    Article  CAS  Google Scholar 

  10. Perera FP, Mayer J, Jaretzki A, Hearne S, Brenner D, Young TL, Fischman HK, Grimes M, Grantham S, Tang MX, Tsai W-Y, Santella RM: Comparison of DNA adducts and sister chromatid exchange in lung cancer cases and controls. Cancer Res 49:4446–4451, 1989.

    CAS  Google Scholar 

  11. van Schooten FJ, Hillebrand MJX, van Leeuwen FE, van Zandwijk N, Jansen HM, den Engelse L, Kriek E: Polycyclic aromatic hydrocarbon-DNA adducts in white blood cells from lung cancer patients: no correlation with adduct levels in lung. Carcinogenesis 13:987–993, 1992.

    Article  Google Scholar 

  12. Shah GM, Bhattacharya RK: Inhibition by 1-ascorbate of binding to DNA of benzo(a)pyrene and its metabolites. Indian J Biochem & Biophysics 17:96–98, 1980.

    CAS  Google Scholar 

  13. Nomi S, Matsuura T, Ueyama H, Ueda K: Effect of vitamin A compounds on the covalent binding of benzo(a)pyrene to nuclear macromolecules. J Nutr Sci Vitaminol 27:33–41, 1981.

    Article  CAS  Google Scholar 

  14. Raina V, Gurtoo HL: Effects of vitamins A, C and E on aflatoxin 81 (AFB1) and benzo[a]pyrene (BP)-induced mutagenesis in Salmonella typhimurium TA-98 and TA-100. Proc Am Assoc Cancer Res 22:112, 1982.

    Google Scholar 

  15. Smalls R, Patterson RM: Reduction of benzo[a]pyrene induced chromosomal aberrations by DL-Alpha tocopherol. Eur J Cell Biol 28:92–97, 1982

    CAS  Google Scholar 

  16. Rocchi P, Arfellini G, Capucci A, Grilli MP: Effect of vitamin A palmitate on mutagenesis induced by polycyclic aromatic hydrocarbons in human cells. Carcinogenesis 4:245–247, 1983.

    Article  CAS  Google Scholar 

  17. Dogra SC, Khanduja KL, Gupta MP: The effect of vitamin A deficiency on the initiation and postinitiation phases of benzo[a]pyrene-induced lung tumorigenesis in rats. Br J Comm 52:931–935, 1985.

    CAS  Google Scholar 

  18. Kallistratos G, Fasske E: Inhibition of benzo[a]pyrene carcinogenesis in rats with vitamin C. J Cancer Res Clin Oncol 97:91–96, 1980.

    Article  CAS  Google Scholar 

  19. McCarthy DJ, Lindamood III C, Hill DL: Effects of retinoids on metabolizing enzymes and on binding of benzo(a)pyrene to rat tissue DNA. Cancer Res 47:5014–5020, 1987.

    CAS  Google Scholar 

  20. Block G, Patterson B, Subar A: Fruit, vegetables, and cancer prevetion: A review of the epidemiological evidence. Nutr Cancer 18:1–29, 1992.

    Article  CAS  Google Scholar 

  21. Santella RM, Gasparro FP, Hsieh LL: Quantitation of carcinogen-DNA adducts with monoclonal antibodies. Prog Exp Tumor Res 31: 63–75, 1987.

    CAS  Google Scholar 

  22. Weston A, Trivers G, Vahakangas K, Newman M, Rowe M: Detection of carcinogen-DNA adducts in human cells and antibodies to these adducts in human sera. Prog Exp Tumor Res 31:76–85, 1987.

    CAS  Google Scholar 

  23. Seidegard J, Pero RW, Miller DG, Beattie EJ: A glutathione transferase in human leukocytes as a marker for the susceptibility to lung cancer. Carcinogenesis 7:751–753, 1986.

    Article  CAS  Google Scholar 

  24. Zhong S, Howie AF, Ketterer B, Taylor J, Hayes JD, Beckett GJ, Wathen CG, Wolf CR, Spurr NK: Glutathione S-transferase mu locus: use of genotyping and phenotyping assays to assess association with lung cancer susceptibility. Carcinogenesis 9:1533–1537, 1991.

    Article  Google Scholar 

  25. Kihara M, Kihara M, Noda K, Okamoto N: Increased risk of lung cancer in Japanese smokers with class mu glutathione S-transferase gene deficiency. Cancer Lett 71:151–155, 1993.

    Article  CAS  Google Scholar 

  26. Nazar-Stewart V, Motulsky AG, Eaton DL, White E, Hornung SK, Leng Z-T, Stapleton P, Weiss NS: The glutathione S-transferase p polymorphism as a marker for susceptibility to lung carcinoma. Cancer Res 53:2313–2318, 1993.

    CAS  Google Scholar 

  27. Bell DA, Taylor JA, Paulson DF, Robertson CN, Mohler JL, Lucier GW: Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer. J Natl Cancer Inst 85:1159–1164, 1993.

    Article  CAS  Google Scholar 

  28. Shields PG, Bowman ED, Harrington AM, Doan VT, Weston A: Polycyclic aromatic hydrocarbon-DNA adducts in human lung and cancer susceptibility genes. Cancer Res 53:3486–3492, 1992.

    Google Scholar 

  29. Willet WC, Stampfer MJ, Underwood BA, Speizer FE, Rosner B, Hennekens CH: Validation of a dietary questionnaire with plasma carotenoid and a-tocopherol levels. Am J Clin Nutr 38:631–639, 1983.

    Google Scholar 

  30. Santella RM, Weston A, Perera FP, Trivers GT, Harris CC, Young TL, Nguyen D, Lee BM, Poirier MC: Interlaboratory comparison of antisera and immunoassays for benzo(a)pyrene-diol-epoxide- I-modified DNA. Carcinogenesis 9 1265–1269, 1988.

    Article  CAS  Google Scholar 

  31. Poirier MC, Santella R, Weinstein IB, Grunberger D, Yuspa SH: Quantitation of benzo[a]pyrene-deoxyguanosine adducts by radioimmunoassay. Cancer Res 40:412–416, 1980.

    CAS  Google Scholar 

  32. Poirier MC: Development of Immunoassays for the Detection of Carcinogen-DNA Adducts. In Molecular Dosimetry and Human Cancer: Analytical Epidemological, and Social Considerations, Groopman JD, Skipper PL, (ed). CRC Press, Boca Raton, 211–230, 1991.

    Google Scholar 

  33. Craft NE, Brown ED, Smith JC: Effects of storage and handling on concentrations of individual carotenoids, retinol, and tocopherol in plasma. Clin Chem 34:44–48, 1988.

    CAS  Google Scholar 

  34. Roe JH, Keuther CA: The determination of ascorbic acid in whole blood and urine through the 2,4-dinitrophenylhydrazine derivative of dehydroascorbic acid. J Biol Chem 147:399, 1943.

    CAS  Google Scholar 

  35. Machacek DA, Jiang NS: Quantitation of cotinine in plasma by liquid chromatography. Clin Chem 32: 979–982, 1986.

    CAS  Google Scholar 

  36. Longnecker MP, Martin-Moreno JM, Knekt P, Nomura AMY, Schober SE, Stahelin HB, Wald NJ, Gey F, Willett WC: Serum a-tocopherol concentration in relation to subsequent colorectal Cancer: pooled data from five cohorts. J. Natl. Cancer Inst 84:430–435, 1992.

    Article  CAS  Google Scholar 

  37. Willet WC, Polk BF, Underwood BA, Stampfer MJ, Pressel S, Rosner B, Taylor JO, Schnider K, Hames, CG: Relation of serum vitamins A and E and carotenioids to the risk of cancer. N Engl J Med 310: 430–434, 1984.

    Google Scholar 

  38. Craig WY, Palomaki GE, Haddow JE: Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data. Br Med J 298:784–8, 1989.

    Article  CAS  Google Scholar 

  39. Shectman G: Estimating ascorbic acid requirements for cigarette smokers. Ann NY Acad Sci 686:335–345 1993.

    Article  Google Scholar 

  40. van Poppel G, Verhagen H, van’t Veer P, van Bladeren PJ: Markers for cytogentic damage in smokers: associations with plasma antioxidants and glutathione S-transferase p. Cancer Epi Biomark Preven 2:441–447, 1993.

    Google Scholar 

  41. Miyamoto H, Araya Y, Ito M, Isobe H, Dosaka H, Shimizu T, Kishi F, Yamamato I, Honma H, Kawakami Y: Serum selenium and vitamin A concentrations in families of lung cancer patients. Carcinogenesis, 60: 1159–1162, 1987.

    CAS  Google Scholar 

  42. Lopez SA, LeGardeur BY: Vitamins A, C and E in relation to lung cancer incidence. Am J Clin Nutr 35:851, 1982.

    Google Scholar 

  43. Rougereau A, Person 0, Rougereau G: Retinol, n-carotene and a-tocopherol status in a French population of healthy subjects. Int J Vitam Nutr Res 57:31–35, 1987.

    CAS  Google Scholar 

  44. Menkes MS, Comstock GW, Vuilleumier JP, Helsing KJ, Rider AA, Brookmeyer R: Serum B-carotene, vitamins A and E, selenium, and the risk of lung cancer. N Engl J Med 315: 1250–1254, 1986.

    Article  CAS  Google Scholar 

  45. Kok FJ, van Duijn CM, Hoffman A, Vermeeren R, De Bruijn AM, Valkenburg HA: Micronutrients and the risk of lung cancer. Am J Clin Nutr 316:1416, 1987.

    CAS  Google Scholar 

  46. Atukorala S, Basu TK, Dickerson JWT, Donaldson D, Sakula A: Vitamin A, zinc and lung cancer. Carcinogenesis 40:927–31, 1979.

    CAS  Google Scholar 

  47. Nomura AMY, Stemmermann GN, Heilbrun LK, Salkeld RM, Vuilleumier JP: Serum vitamin levels and the risk of cancer of specific sites in men of Japanese ancestry in Hawaii. Cancer Res 45:2369–72, 1985.

    CAS  Google Scholar 

  48. Byers TE, Grahma S. Haughey BP, Marshall JR, Swanson MK: Diet and lung cancer risk: Findings from the Western New York Diet Study. Am J Epidemiol 125: 351–6, 1987.

    CAS  Google Scholar 

  49. Matsuura T, Ueyama H, Nomi S, Ueda K: Effect of a-tocopherol on the binding of benzo[a]pyrene to nuclear macromolecules. J Nutr Sci Vitaminol 25: 495–504, 1979.

    Article  CAS  Google Scholar 

  50. Williams DE, Carpenter HM, Buhler DR, Kelly JD, Dutchuk M: Alterations in lipid peroxidation antioxidant enzymes, and carcinogen metabolism in liver microsomes of vitamine E-deficient trout and rat. Toxicol Appl Pharmacol 116: 78–84, 1992.

    Article  CAS  Google Scholar 

  51. Chen LH, Shiau CC: Induction of glutathione-Stransferase activity by antioxidants in hepatocyte culture. Anticaner Res 9:1069–72, 1989.

    CAS  Google Scholar 

  52. Chen Y-T, Ding H-H: Vitamins E and K induced aryl hydrocarbon hydroxylase activity in human cell cultures. Biochem. Biophys Res Commun 143:863–871, 1987.

    Article  CAS  Google Scholar 

  53. Shekelle RB, Lepper M, Liu S, Maliza C, Raynor WJ, Rossof AH: Dietary vitamin A and risk of cancer in the Wester Electric Study. Lancet 2:1185–90, 1981.

    Article  CAS  Google Scholar 

  54. Kvale G, Bejelke E, Gart JJ: Dietary habits and lung cancer risk. Intl J Cancer 31:397–405, 1983.

    Article  CAS  Google Scholar 

  55. Hinds MW, Kolonel LN, Hawkin JH, Lee J: Dietary vitamin A, carotene, vitamin C and risk of lung cancer in Hawaii. Am J Epidemiol 199:227–37, 1984.

    Google Scholar 

  56. Staehelin HB, Gey KF, Brubacher G: Plasma vitamin C and cancer death: The prospective basel study. Ann NY Acad Sci 498:124–31, 1987.

    Article  CAS  Google Scholar 

  57. Long-De W, Hammond EC: Lung cancer, fruit, green salad and vitamin pills. Chin Med J 98:206–210, 1985.

    Google Scholar 

  58. LeMarChand L, Yoshizawa CN, Kolonel LN, Hankin JH, Goodman MT: Vegetable consumption and lung cancer risk: A population based case-control study in Hawaii. J Natl Cancer Inst 81: 1158–1164, 1989.

    Article  CAS  Google Scholar 

  59. Kromhout D: Essential micronutrients in relation to carcinogenesis. Am J Clin Nutr 45:1361–1367, 1987.

    CAS  Google Scholar 

  60. Hoefel OS: Smoking: An important factor in vitamin C deficiency. Int J Vitam Nutr Res Suppl 24:121–124, 1983.

    CAS  Google Scholar 

  61. Belvedere G, Miller H, Vatsis KP, Coon MJ, Gelboin HV: Hydroxylation of benzo[a]pyrene and binding of (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene metabolites to deoxyribonucleic acid catalyzed by purified forms of liver microsomal cytochrome P-450. Biochem Pharm 29:1693–702, 1980.

    Article  CAS  Google Scholar 

  62. Kiyohara C, Omura M, Hirohata T: In vitro effects of L-ascorbic acid (vitamin C) on aryl hydrocarbon hydroxylase activity in hepatic microsomes of mice. Mutat Res 251:227–32, 1991.

    Article  CAS  Google Scholar 

  63. Nebert DW: Role of genetics and drug metabolism in human cancer risk. Mutat Res 247:267–281, 1991.

    Article  CAS  Google Scholar 

  64. Geneste 0, Camus A-M, Castegnaro M, Petruzzelli S, Macchiarine P, Angeletti CA, Giuntini C, Bartsch H: Comparison of pulmonary DNA adduct levels, measured by 32P-postlabelling and aryl hydrocarbon hydroxylase activity in lung parenchyma of smokers and ex-smokers. Carcinogenesis 12:1301–1305, 1991.

    Article  CAS  Google Scholar 

  65. Manchester DK, Bowman ED, Parker NB, Caporaso NE, and Weston A: Determinants of polycyclic aromatic hydrocarbon-DNA adducts in human placenta. Cancer Res 52:1499–503, 1992.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hoffmann-La Roche, NJ, Nutley, 07110, USA

    Ricardo A. Grinberg-Funes & Vishwa N. Singh

  2. Columbia Presbyterian Cancer Center and Columbia School of Public Health, N.Y., NY, 10032, USA

    Frederica P. Perera, Tie Lan Young, Christopher Dickey, Lian W. Wang & Regina M. Santella

  3. National Institute of Environmental Health Science, Research Triangle Park, NC, 27709, USA

    Douglas A. Bell

Authors
  1. Ricardo A. Grinberg-Funes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vishwa N. Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frederica P. Perera
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Douglas A. Bell
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tie Lan Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christopher Dickey
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lian W. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Regina M. Santella
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Colorado Health Sciences Center, Denver, CO, USA

    Kedar N. Prasad PhD

  2. University of Pavia, Italy

    Leonida Santamaria MD

  3. Cancer Treatment Center of America, Des Moines, IA, USA

    R. Michael Williams MD, PhD

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer Science+Business Media New York

About this chapter

Cite this chapter

Grinberg-Funes, R.A. et al. (1995). Polycyclic Aromatic Hydrocarbon-DNA Adducts in Smokers and Their Relationship to Micronutrient Levels and Glutathione-S-Transferase M1 Genotype. In: Prasad, K.N., Santamaria, L., Williams, R.M. (eds) Nutrients in Cancer Prevention and Treatment. Experimental Biology and Medicine, vol 27. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4612-0237-0_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-0237-0_12

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4612-6675-4

  • Online ISBN: 978-1-4612-0237-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation